CN104513201A - Crystal of pixantrone maleate - Google Patents
Crystal of pixantrone maleate Download PDFInfo
- Publication number
- CN104513201A CN104513201A CN201310452883.5A CN201310452883A CN104513201A CN 104513201 A CN104513201 A CN 104513201A CN 201310452883 A CN201310452883 A CN 201310452883A CN 104513201 A CN104513201 A CN 104513201A
- Authority
- CN
- China
- Prior art keywords
- crystallization
- crystal
- toxilic acid
- china fir
- fine jade
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- PEZPMAYDXJQYRV-UHFFFAOYSA-O NCCNc(c(C(c1c2ccnc1)=O)c1C2=O)ccc1NCC[NH3+] Chemical compound NCCNc(c(C(c1c2ccnc1)=O)c1C2=O)ccc1NCC[NH3+] PEZPMAYDXJQYRV-UHFFFAOYSA-O 0.000 description 2
- 0 NCC*c(c(C(c1cnccc11)=O)c2C1=O)ccc2NCCN Chemical compound NCC*c(c(C(c1cnccc11)=O)c2C1=O)ccc2NCCN 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D221/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00
- C07D221/02—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00 condensed with carbocyclic rings or ring systems
- C07D221/04—Ortho- or peri-condensed ring systems
- C07D221/06—Ring systems of three rings
- C07D221/08—Aza-anthracenes
Abstract
The invention belongs to the field of pharmaceutical chemistry, and particularly relates to a crystal of pixantrone maleate, a preparation method of the crystal, a pharmaceutical composition containing the crystal, and an application of the crystal in the field of medicines. The crystal provided by the invention has high purity, good stability at high temperature and high humidity, good powder fluidity and capability of meeting the requirements of preparation and production of medicaments.
Description
Technical field
The invention belongs to medicinal chemistry art, in particular to the preparation method of the crystallization of a toxilic acid China fir fine jade, described crystallization, the pharmaceutical composition containing described crystallization and the purposes at field of medicaments.
Background technology
A toxilic acid China fir fine jade, chemistry by name 6,9-two [(2-amino-ethyl) is amino]-benzo [g] isoquinoline 99.9-5,10-diketone 2-maleate, structure is such as formula shown in I, be developed by Novas Pharmaceutical S.P.A and the s-generation azepine anthraquinone analogue gone on the market, in May, 2012 is granted in Europe is used for the treatment of non Hodgkin lymphom (NHL), and in September, 2012 in Sweden, Denmark and Finland's listing.
A.Marini et al, Solid-State Characterization of a Novel Chemotherapeutic Drug, Journal ofPharmaceutical Sciences, Vol.92,577-584 (2003) discloses the characterization data of the crystallization (hereinafter referred to as I type crystallization) of a kind of toxilic acid China fir fine jade, it contains 1.5 crystal water, and discloses its X-ray diffracting spectrum.
The change of medicinal compound crystal formation causes compound to have different fusing points, solubleness, water absorbability, stability, biological activity etc. usually, and these are all the important factors affecting difficulty or ease, stability in storage, preparation difficulty or ease and bioavailability etc. prepared by medicine.When there is polymorphic in compound, because specific polymorphic form has specific thermodynamic property and stability, therefore, in the process of preparation, the crystal formation understanding the compound applied in each formulation is important, to ensure the medicine of process application same modality.Therefore, ensure that compound be single crystal formation or the known miscellany of some crystal formations is necessary.
When judging which kind of polymorphic form is preferred, their much character must be compared and preferred polymorphic form makes one's options based on many physical propertiess.Preferred under completely likely the difficulty or ease, stability etc. of a kind of polymorphic in some aspects as preparation are considered to critical condition.In other cases, different polymorphic form may the solubleness of Yin Genggao or excellent pharmacokinetics and preferably.
The discovery of the new polymorphic form of medicinal compound provides the chance improving medicine physical property, namely whole character of material are extended, thus the research of compound and preparation thereof can be instructed better, therefore the polymorphic form of a toxilic acid provided by the invention China fir fine jade has commercial value in the manufacture and other application of medicine.
Summary of the invention
One aspect of the present invention provides two kinds of crystalline solid forms of the China fir fine jade of the toxilic acid shown in formula I, is respectively II type crystallization and III type crystallization.
Wherein II type crystallization refers to the crystallization being substantially free of crystal water and/or other solvent, use Cu-K α radiation, it is in X-ray powder diffraction (XRD) collection of illustrative plates, 8.65 are about at the 2 θ number of degrees, 9.49, 10.30, 17.42, 18.70, 26.37 there is diffraction peak at place, typically be about 8.65 at the 2 θ number of degrees, 9.49, 10.30, 17.42, 18.70, 21.39, 25.05, 26.37, 28.38, 28.83 there is diffraction peak at place, typically be about 8.65 at the 2 θ number of degrees further, 9.49, 10.30, 13.12, 14.05, 14.19, 15.65, 16.31, 17.42, 18.70, 19.89, 21.39, 22.48, 25.05, 26.37, 28.38, 28.83 there is diffraction peak at place.
Use Cu-K α radiation, the spectrogram of the typical XRD of II type crystallization has following feature:
| Numbering | 2 θ (degree) | Relative intensity (%) |
| 1 | 8.65 | 100.0 |
| 2 | 9.49 | 16.0 |
| 3 | 10.30 | 31.9 |
| 4 | 13.12 | 3.0 |
| 5 | 14.05 | 5.7 |
| 6 | 14.19 | 4.8 |
| 7 | 15.65 | 4.9 |
| 8 | 16.31 | 5.8 |
| 9 | 17.42 | 47.3 |
| 10 | 18.70 | 30.1 |
| 11 | 19.89 | 4.9 |
| 12 | 21.39 | 15.2 |
| 13 | 22.48 | 4.5 |
| 14 | 25.05 | 11.7 |
| 15 | 26.37 | 68.1 |
| 16 | 28.38 | 22.9 |
| 17 | 28.83 | 23.6 |
In one embodiment of the invention, II type crystallization has powder x-ray diffraction collection of illustrative plates as shown in Figure 2 substantially.
II type crystallization prepares by following method, and it comprises the following steps: a) mixed with anhydrous methanol by a toxilic acid China fir fine jade, from anhydrous methanol, b) be separated II type crystallization.
Wherein step a) in the amount of anhydrous methanol be advisable so that a toxilic acid China fir fine jade can be dissolved completely.Optionally, abundant stirring and crystallizing can be carried out.In one embodiment of the invention, stir at 20-40 DEG C, churning time is preferably 2-3 hour.
Step b) in be separated obtain crystallization after, can further drying.In one embodiment of the invention, carry out air blast oven dry at 55 ~ 65 DEG C, time of drying is preferably 6-10 hour.
III type crystallization refers to the crystallization being substantially free of crystal water and/or other solvent, use Cu-K α radiation, it is in X-ray powder diffraction (XRD) collection of illustrative plates, 9.95 are about at the 2 θ number of degrees, 10.95, 15.52, 16.51, 18.94, 19.76, 26.80 there is diffraction peak at place, typically be about 9.95 at the 2 θ number of degrees, 10.95, 15.52, 16.51, 18.33, 18.94, 19.76, 21.77, 26.40, 26.80, 27.46, 28.08 there is diffraction peak at place, typically be about 8.30 at the 2 θ number of degrees further, 9.95, 10.95, 13.15, 14.23, 15.52, 16.51, 18.33, 18.94, 19.76, 21.77, 26.40, 26.80, 27.46, 28.08, 31.53 there is diffraction peak at place.
Use Cu-K α radiation, the spectrogram of the typical XRD of III type crystallization has following feature:
| Numbering | 2 θ (degree) | Relative intensity (%) |
| 1 | 8.30 | 2.9 |
| 2 | 9.95 | 30.0 |
| 3 | 10.95 | 29.2 |
| 4 | 13.15 | 3.7 |
| 5 | 14.23 | 4.4 |
| 6 | 15.52 | 23.0 |
| 7 | 16.51 | 46.4 |
| 8 | 17.05 | 3.2 |
| 9 | 18.33 | 8.3 |
| 10 | 18.94 | 24.9 |
| 11 | 19.76 | 21.0 |
| 12 | 21.04 | 2.1 |
| 13 | 21.77 | 18.4 |
| 14 | 25.39 | 2.2 |
| 15 | 26.40 | 22.0 |
| 16 | 26.80 | 100.0 |
| 17 | 27.46 | 23.1 |
| 18 | 28.08 | 31.2 |
| 19 | 31.53 | 10.3 |
In one embodiment of the invention, III type crystallization has powder x-ray diffraction collection of illustrative plates as shown in Figure 3 substantially.
III type crystallization prepares by following method, and it comprises the following steps: a) mixed with dehydrated alcohol by a toxilic acid China fir fine jade, b) separating III type crystallization from dehydrated alcohol.
Wherein step a) in the amount of dehydrated alcohol be advisable so that a toxilic acid China fir fine jade can be dissolved completely.Optionally, stirring and crystallizing can be carried out.In one embodiment of the invention, stir at 20-40 DEG C, churning time is preferably 8-12 hour.
Step b) in be separated obtain crystallization after, can further drying.In one embodiment of the invention, carry out air blast oven dry at 55 ~ 65 DEG C, time of drying is preferably 6-10 hour.
Powder x-ray diffraction test of the present invention is carried out according to following condition:
Bruker D8ADVANCE instrument is adopted to measure.Test condition is as follows: light source, CuK α 40kV40mA, graphite monochromator, divergent slit (DS): 1 °; Antiscatter slits (SS): 1 °; LynxEye detector array, scan mode: θ/θ, continuous sweep; Sweep limit: 5 °-40 °, sweep velocity 8 °/min.
It should be noted that, in XRD, the diffraction spectrogram obtained by crystalline compounds is distinctive often for specific crystal formation, wherein the relative intensity of bands of a spectrum (especially at low angle) the advantage orientation effect that may produce because of the difference of crystallization condition, particle diameter and other condition determination and changing.Therefore, the relative intensity of diffraction peak to for crystal formation be not distinctive, when judging whether identical with known crystal formation, should be noted that relative position instead of their relative intensity at peak.Usually peak position is represented with 2 θ angles or crystal face apart from d in XRD figure spectrum, because 2 θ angles are relevant with the wavelength of incident X-rays, have simple conversion relation between the two: d=λ/2sin θ, wherein d represents crystal face distance, λ represents the wavelength of incident X-rays (for Cu-Ka
), θ is diffraction angle.For the crystal formation of the same race of same compound, its XRD spectra has similarity on the whole, characterize 2 θ angular errors of peak position generally within ± 2%, such as, because the change of temperature during analytic sample, sample move or the demarcation etc. of instrument, the position at peak may be moved; Relative intensity error can be comparatively large, but variation tendency is consistent.In addition, should note keeping organic conception when judging that whether crystal formation is the same, because be not that a diffracted ray represents a thing phase, but a set of specific " d-I/I1 " data just represent a certain thing phase.Should be noted also that in the qualification of mixture, because under content, degradation factor can cause the disappearance of portion diffracts line, now, without the need to relying in high-purity sample the whole bands of a spectrum observed, even several bands of a spectrum may be also distinctive to given crystallization.
The present invention provides the crystal composition of above-mentioned II type crystallization or III type crystallization on the other hand.Wherein the crystal composition of II type crystallization refers to, in composition, II type crystallization accounts for more than 50% of composition weight, preferably more than 80%, more preferably more than 90%, most preferably more than 95%, other crystallization or the amorphous article of a small amount of formula I can be contained in said composition, include but not limited to I type crystallization of formula I, III type crystallization or amorphous article.
The crystal composition of III type crystallization refers to, III type crystallization of the formula I in composition accounts for more than 50% of composition weight, preferably more than 80%, more preferably more than 90%, most preferably more than 95%, other crystallization or the amorphous article of a small amount of formula I can be contained in said composition, include but not limited to II type crystallization of formula I, I type crystallization or amorphous article.
Further aspect of the present invention provides a kind of pharmaceutical composition, and it comprises above-mentioned crystallization or crystal composition.Optional, described pharmaceutical composition also can comprise pharmaceutically acceptable auxiliary material.
Pharmaceutical composition of the present invention can be selected from various type, such as tablet, capsule, powder injection, injection etc.The auxiliary material being applicable to these concrete formulations is well known in the art, and such as tablet generally includes thinner (such as starch, lactose, Microcrystalline Cellulose, N.F,USP MANNITOL), wetting agent and tamanori (such as hydroxypropylcellulose, hypromellose, polyvidone), disintegrating agent (such as carboxymethylstach sodium, low-substituted hydroxypropyl cellulose, polyvinylpolypyrrolidone), lubricant (such as Magnesium Stearate, micropowder silica gel, talcum powder); Powder injection generally includes propping agent (such as N.F,USP MANNITOL, lactose, dextran, sodium-chlor), pH adjusting agent (such as hydrochloric acid, sodium hydroxide).In addition, the method preparing these concrete formulations is also well known in the art, and such as tablet can adopt wet granule compression tablet method, compressing dry granulation, direct powder compression etc. to be prepared; The preparation method of powder injection generally includes preparation, filtration, filling, pre-freeze, sublimation drying, again drying and other steps.
Pharmaceutical composition of the present invention is by various ways administration, and administering mode includes but not limited to intravenously, intraperitoneal, subcutaneous, intramuscular or oral administration, preferably adopts the mode of intravenous administration or oral administration.Administration frequency is once a day, once in a week, biweekly or monthly, and preferably with the pharmaceutical composition administration of single dose form, the pharmaceutical composition of described single dose form comprises a toxilic acid China fir fine jade II type crystallization or the III type crystallization of 1mg-250mg.
In a specific embodiments of the present invention, the pharmaceutical composition of single dose form is powder injection, and it comprises a toxilic acid China fir fine jade II type crystallization of 50mg, sodium-chlor, lactose and pH adjusting agent.
In another specific embodiments of the present invention, the pharmaceutical composition of single dose form is powder injection, and it comprises a toxilic acid China fir fine jade III type crystallization of 50mg, sodium-chlor, lactose and pH adjusting agent.
Further aspect of the present invention provides above-mentioned crystallization, crystal composition or pharmaceutical composition preparing the purposes in anti-tumor drug, the purposes especially in the medicine of the anti-non Hodgkin lymphom of preparation.
Crystallization provided by the invention, not only purity is high, and when high temperature, high humidity good stability, there is good powder fluidity, meet medicine preparation, produce requirement.
Accompanying drawing explanation
Fig. 1: the powder x-ray diffraction collection of illustrative plates of a toxilic acid China fir fine jade I type crystallization prepared by the embodiment of the present invention 1.
Fig. 2: the powder x-ray diffraction collection of illustrative plates of a toxilic acid China fir fine jade II type crystallization prepared by the embodiment of the present invention 2.
Fig. 3: the powder x-ray diffraction collection of illustrative plates of a toxilic acid China fir fine jade III type crystallization prepared by the embodiment of the present invention 3.
Embodiment
Below in conjunction with specific embodiment, the present invention is conducted further description, but in the present invention, these embodiments and other embodiments only do not limit the scope of the invention for illustrating.
The preparation of an embodiment 1 toxilic acid China fir fine jade I type crystallization
Disclosed in the embodiment 1 of CN1145028, method prepares a toxilic acid China fir fine jade.
As shown in Figure 1, this spectrogram is substantially identical with (a) in the Figure4 of foreign language literature Solid-State Characterization of aNovel Chemotherapeutic Drug, is I type crystallization for powder x-ray diffraction collection of illustrative plates.
The preparation of an embodiment 2 toxilic acid China fir fine jade II type crystallization
The China fir fine jade I type crystallization of 3g toxilic acid is dissolved in 30ml anhydrous methanol, fully stirs 3 hours at 30 DEG C, filter, by filter cake in 60 DEG C of forced air dryings 6 hours, obtain 2.5g Dark blue crystals powder.
The purity that HPLC area normalization method measures is 99.88%.
Powder x-ray diffraction collection of illustrative plates as shown in Figure 2.
The preparation of an embodiment 3 toxilic acid China fir fine jade III type crystallization
The China fir fine jade I type crystallization of 5g toxilic acid is dissolved in 60ml dehydrated alcohol, fully stirs 10 hours at 35 DEG C, filter, by filter cake in 60 DEG C of forced air dryings 6 hours, obtain 4.4g Dark blue crystals powder.
The purity that HPLC area normalization method measures is 99.85%.
Powder x-ray diffraction collection of illustrative plates as shown in Figure 3.
Embodiment 4 stability experiment
With reference to the Acceleration study of Chinese Pharmacopoeia version in 2010 two annex XIX C and the method for long-term experiment, get III type crystallization of I type crystallization of appropriate embodiment 1 gained, II type crystallization of embodiment 2 gained and embodiment 3 gained, after carrying out long-term and Acceleration study, by following HPLC condition, related substance is measured.
Instrument: Agilent1100; Chromatographic column: C18,4.6 × 150mm, 5 μm; Column temperature: 25 DEG C; Determined wavelength: 245nm; Flow velocity: 1.0ml/min; Moving phase: with 20mM heptane sulfonic acid sodium salt for mobile phase A, take acetonitrile as Mobile phase B, according to the form below carries out linear gradient elution,
| Time (minute) | Mobile phase A (%) | Mobile phase B (%) |
| 0 | 80 | 20 |
| 5 | 80 | 20 |
| 40 | 70 | 30 |
| 55 | 50 | 50 |
| 60 | 50 | 50 |
Experimental result:
Accelerate and long-term test results
And after measured, II type crystallization before test and after test, III type crystallization, only stop angle θ all≤30 °, there is good mobility, meet the demand of producing and in production process.
Claims (10)
1. the crystallization of the toxilic acid China fir fine jade shown in formula I, use Cu-K α radiation, it is in X-ray powder diffraction, and being about 8.65,9.49,10.30,17.42,18.70,26.37 places at the 2 θ number of degrees has diffraction peak,
2. crystallization according to claim 1, being about 8.65,9.49,10.30,17.42,18.70,21.39,25.05,26.37,28.38,28.83 places at the 2 θ number of degrees has diffraction peak.
3. crystallization according to claim 1, being about 8.65,9.49,10.30,13.12,14.05,14.19,15.65,16.31,17.42,18.70,19.89,21.39,22.48,25.05,26.37,28.38,28.83 places at the 2 θ number of degrees has diffraction peak.
4. the crystallization of the toxilic acid China fir fine jade shown in formula I, use Cu-K α radiation, it is in X-ray powder diffraction, and being about 9.95,10.95,15.52,16.51,18.94,19.76,26.80 places at the 2 θ number of degrees has diffraction peak,
5. crystallization according to claim 4, being about 9.95,10.95,15.52,16.51,18.33,18.94,19.76,21.77,26.40,26.80,27.46,28.08 places at the 2 θ number of degrees has diffraction peak.
6. crystallization according to claim 4, being about 8.30,9.95,10.95,13.15,14.23,15.52,16.51,18.33,18.94,19.76,21.77,26.40,26.80,27.46,28.08,31.53 places at the 2 θ number of degrees has diffraction peak.
7. crystal composition, the crystallization of the toxilic acid China fir fine jade wherein according to any one of claim 1-6 accounts for more than 50% of crystal composition weight, preferably more than 80%, more preferably more than 90%, most preferably more than 95%.
8. pharmaceutical composition, it comprises the crystallization of the toxilic acid China fir fine jade according to any one of claim 1-6 or crystal composition according to claim 7.
9. the crystallization of the toxilic acid China fir fine jade according to any one of claim 1-6, crystal composition according to claim 7 or pharmaceutical composition according to claim 8 are preparing the purposes in anti-tumor drug.
10. purposes according to claim 9, wherein said tumour is non Hodgkin lymphom.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310452883.5A CN104513201B (en) | 2013-09-28 | 2013-09-28 | Crystal of pixantrone maleate |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310452883.5A CN104513201B (en) | 2013-09-28 | 2013-09-28 | Crystal of pixantrone maleate |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN104513201A true CN104513201A (en) | 2015-04-15 |
| CN104513201B CN104513201B (en) | 2017-12-26 |
Family
ID=52789105
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201310452883.5A Active CN104513201B (en) | 2013-09-28 | 2013-09-28 | Crystal of pixantrone maleate |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN104513201B (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105699548A (en) * | 2015-12-11 | 2016-06-22 | 海南通用康力制药有限公司 | Method for analysis and detection of maleic acid pixantrone through high performance liquid chromatography |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0503537A1 (en) * | 1991-03-08 | 1992-09-16 | The University Of Vermont | 6,9 Bis(substituted-amino)benzo-[g]isoquinoline-5,10-diones |
| CN1145028A (en) * | 1994-03-28 | 1997-03-12 | 泊灵格曼海姆意大利股份公司 | A improved method of synthesis for 6,9-bis[(2-aminoethyl)amino] benzo[g] isoquinoline-5,10-dione and its dimaleate salt |
-
2013
- 2013-09-28 CN CN201310452883.5A patent/CN104513201B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0503537A1 (en) * | 1991-03-08 | 1992-09-16 | The University Of Vermont | 6,9 Bis(substituted-amino)benzo-[g]isoquinoline-5,10-diones |
| CN1145028A (en) * | 1994-03-28 | 1997-03-12 | 泊灵格曼海姆意大利股份公司 | A improved method of synthesis for 6,9-bis[(2-aminoethyl)amino] benzo[g] isoquinoline-5,10-dione and its dimaleate salt |
Non-Patent Citations (3)
| Title |
|---|
| A. PAUL KRAPCHO ET AL.,: "6,9-Bis[(aminoalkyl)amino]benzo[g]isoquinoline-5,l0-diones. A Novel Class of Chromophore-Modified Antitumor Anthracene-9,l0-diones: Synthesis and Antitumor Evaluations", 《J. MED. CHEM.》 * |
| LOLLI, FRANCESCO ET AL.,: "Topoisomerase II inhibitor DNA intercalating agent oncolytic", 《DRUGS OF THE FUTURE》 * |
| REWCASTLE, GORDON W.: "BBR-2778. Boehringer Mannheim GmbH", 《CURRENT OPINION IN ONCOLOGIC, ENDOCRINE & METABOLIC INVESTIGATIONAL DRUGS》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105699548A (en) * | 2015-12-11 | 2016-06-22 | 海南通用康力制药有限公司 | Method for analysis and detection of maleic acid pixantrone through high performance liquid chromatography |
Also Published As
| Publication number | Publication date |
|---|---|
| CN104513201B (en) | 2017-12-26 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU2011213431B2 (en) | Polymorphs of dasatinib, preparation methods and pharmaceutical compositions thereof | |
| CN112142679B (en) | Gefitinib and vanilloid eutectic methanol solvate and preparation method thereof | |
| CN102336801B (en) | Abiraterone acetate polymorphic substance and pharmaceutical composition | |
| CN104109124B (en) | The rich crystal for Buddhist nun 0.5 malate of card | |
| CN104761492A (en) | Crystal form of sorafenib tosylate, and preparation method thereof | |
| CN104045615B (en) | (1S) crystal form A and its preparation method and application of-1-[the chloro-3-of 4-(4-ethoxy benzyl) phenyl]-1,6-dideoxy-D-Glucose | |
| CN102558275A (en) | Alpha type polycrystalline abiraterone acetate crystal, and preparation method, application and pharmaceutical composition thereof | |
| CN104513201A (en) | Crystal of pixantrone maleate | |
| CN107245054B (en) | Amorphous bulleyaconitine A compound and preparation method thereof | |
| CN113651770B (en) | Epalrestat crystal form, and preparation method and application thereof | |
| AU2021106179A4 (en) | New crystalline form of epalrestat as well as preparation method and application thereof | |
| CN103073543A (en) | Preparation method and application of tropisetron citrate crystal form I | |
| CN111303124A (en) | Novel crystal of oxitinib mesylate | |
| CN110563644A (en) | Novel crystal form of Lunvatinib mesylate | |
| CN104693192A (en) | Crystal form A of compound as well as preparation method and application thereof | |
| CN112608328B (en) | Crystal form of 5-bromotetrandrine ethyl formate and preparation method thereof | |
| CN112552308B (en) | 5-bromo-bis-demethyltetrandrine ethyl formate crystal form and preparation method thereof | |
| CN111423418A (en) | Amorphous compound of oxitinib mesylate and pharmaceutical composition thereof | |
| CN101591323B (en) | Five crystal forms of 7-hydroxy-isoflavone, preparation method thereof, medicine composition thereof and application | |
| CN112625047B (en) | Crystal form of fangchinoline-7-propionate and preparation method thereof | |
| CN111303042A (en) | Novel crystal form of enzalutamide | |
| CN104610208A (en) | (1S)-1,6-dideoxy-1-[4-methoxy-3-(trans-4-n-propylcyclohexyl)methylphenyl]-D-glucopyranose crystal form A, preparation method and applications thereof | |
| CN106554357B (en) | Morphine derivatives crystal form I and its preparation method and application | |
| CN106554377B (en) | Morphine derivatives crystal form III and its preparation method and application | |
| CN106554376B (en) | Morphine derivatives crystal form II and its preparation method and application |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| TR01 | Transfer of patent right | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20191209 Address after: Room 101, training building, Tiankun Wanbei economic and technological school, southeast corner, intersection of Xiaguang Avenue and 204 provincial road, Tianqiao sub district office, Linquan County, Fuyang City, Anhui Province, 236000 Patentee after: Linquan Bailiang Electronic Information Technology Co., Ltd Address before: 222006 No. 8 Julong North Road, Sinpo District, Jiangsu, Lianyungang Patentee before: Chia Tai Tianqing Pharmaceutical Group Co., Ltd. |
|
| TR01 | Transfer of patent right | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20220525 Address after: 300000 building 4, No. 16, Wujing Road, Dongli Development Zone, Dongli District, Tianjin Patentee after: TIANJIN GUOKE YIGONG TECHNOLOGY DEVELOPMENT Co.,Ltd. Address before: 236000 Room 101, training building, Tiankun Wanbei economic and technological school, southeast corner of intersection of Xiaguang Avenue and 204 provincial road, Tianqiao Street office, Linquan County, Fuyang City, Anhui Province Patentee before: Linquan Bailiang Electronic Information Technology Co.,Ltd. |